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Flashcards in Protein Folding 3 Deck (44):
1

What is the size of ubiquitin?

76aa

2

What is ubiquitin used for?

Tagging proteins for degradations in the proteasome pathway.

3

How ubiquitin linked to proteins?

Using an isopeptide bond via Lys 48, Lys 63 and N terminus.

4

Which protein complex tags protein with ubiquitin?

E1-E2-E3.

5

Which protein in the complex provides specificity and how?

E3 (protein ligase complex) - interacts with protein and ubiquitin.

6

What can give variability given to the tag?

poly-ubiquitination

7

What protein does HPV encode and what does it target?

E3 - specific to p53 tumour suppressor protein.

8

What proteins recognise misfolded or damaged proteins?

Hsp40-Hsp70 complex.

9

What does recognition by the Hsp40-Hsp70 complex lead to?

This will lead to E1-E2-E3 complex where poly-ubiquitination will occur via Lys 48 – tagged for degradation.

10

What is the structure of the proteasome?

central chamber - 28 proteins and 2 lids.
Four rings make up central chamber.

11

Which part of proteasome recognise the poly-U tag?

The two lids.

12

Where are proteasomes found?

eukaroyotes, archaea and some bacteria.

13

Which rings function as the gate?

outer two rings.

14

Which proteins recognise misfolded proteins in aggresome-autophagy pathway?

Parkin, Ubc13 and Uev1a.

15

How are misfolded proteins in aggresome-autophaphy pathway tagged?

Ubiquitin via Lys 63.

16

What does the ubiquitin Lys 63 tag promote?

The binding of p62 which recruits autophagic membranes to aggresome to form autophagosome - fuses with lysosome.

17

What can form amyloid fibrils?

Partially folded intermediates/degraded fragments.

18

Can all types of proteins form amyloids?

yes.

19

What does the fact that all proteins can form amyloid fibrils suggest?

That amyloid fibrils are the real thermodynamic minimum in folding.

20

What % of people have Alzheimers +65 years?

10%

21

What % of people have Alzheimers +85years?

50%

22

What happens to brain tissue that contain amyloid plaques?

they form neurofibrillary tangles.

23

What do protein causes amyloids?

Amyloid Beta peptide.

24

Which protein is Amyloid Beta peptide derived from?

Amyloid beta precursor protein (AbetaPP) - it undergoes proteolysis to form this.

25

What is the pathway of amyloid fibril formations?

Native --> amyloidgenic intermediate --> oligomers --> protofibrils --> amyloid fibrils.

26

What is the most toxic species in pathway?

Oligomers - not structurally defined.

27

Are amyloidgenic precursors (protein monomers) transient?

Yes.

28

Are amyloid fibrils resistant to detergents/unfolding agents?

Yes.

29

What do oligomers have the ability to do?

penetrate cellular membranes.

30

What secondary structure are amyloids made of?

Extended beta sheets.

31

What is distance between beta strands in amyloids?

4.7A

32

What is distance between beta sheets in amyloids?

10.7A

33

What is the steric zipper model referring to in amyloids?

Tight hydrogen bonding between beta strands that excludes water.

34

What did more recent analysis of amyloid structure show?

That they are hollow in middle and this is water filled.

35

What the size of Prion protein and what is it bound to?

208aa and membrane bound.

36

Is prion protein self propagating and what does this mean?

Yes - can convert normal cellular prion protein to scrapie protein.

37

Give examples of diseases caused by Prion gene mutation?

Familial CJD
Fatal familial insomnia.

38

Do IDPs have a large number of minimum energy conformations?

Yes.

39

What are the main properties of IDPs?

Tend to be charged with low hydrophobicity - this drives folding.

40

Why is not good to crystallise IDPs?

Even if possible would only be viewing one possible conformation.

41

What can be used to monitor IDPs?

NMR.

42

Can IDPs have residual secondary structure?

Yes - partial alpha helix, partial beta strand, partial poly-proline helix.

43

What type of helix is a poly proline helix?

Left handed helix - makes turn every 3 residues - pro every 3 residues.

44

What does NMR spectra of IDPs look like?

Limited dispersion - sharp peaks (long T2 - has little dipolar coupling as is unfolded).